JPS5953498A - 5,2',3',4',4",6"-hexadeoxykanamycin and its 1-n-acryl derivative - Google Patents
5,2',3',4',4",6"-hexadeoxykanamycin and its 1-n-acryl derivativeInfo
- Publication number
- JPS5953498A JPS5953498A JP57162292A JP16229282A JPS5953498A JP S5953498 A JPS5953498 A JP S5953498A JP 57162292 A JP57162292 A JP 57162292A JP 16229282 A JP16229282 A JP 16229282A JP S5953498 A JPS5953498 A JP S5953498A
- Authority
- JP
- Japan
- Prior art keywords
- amino
- compound
- group
- water
- mmol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 11
- -1 S-methylthiocarbonyl group Chemical group 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 229930027917 kanamycin Natural products 0.000 claims description 4
- 229960000318 kanamycin Drugs 0.000 claims description 4
- 229930182823 kanamycin A Natural products 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 6
- 241000894006 Bacteria Species 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 5
- 125000003277 amino group Chemical group 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 229940127089 cytotoxic agent Drugs 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 4
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 125000006242 amine protecting group Chemical group 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- JJCQSGDBDPYCEO-XVZSLQNASA-N dibekacin Chemical compound O1[C@H](CN)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N JJCQSGDBDPYCEO-XVZSLQNASA-N 0.000 description 3
- 229960003807 dibekacin Drugs 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 3
- CFOGIGZVKWLSHG-UHFFFAOYSA-N 2-(aminomethyl)-6-[4,6-diamino-3-(4-amino-3,5-dihydroxy-6-methyloxan-2-yl)oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol Chemical compound OC1C(N)C(O)C(C)OC1OC1C(O)C(OC2C(C(O)C(O)C(CN)O2)O)C(N)CC1N CFOGIGZVKWLSHG-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- VOZKAJLKRJDJLL-UHFFFAOYSA-N 2,4-diaminotoluene Chemical group CC1=CC=C(N)C=C1N VOZKAJLKRJDJLL-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- JHHASXMVMHKBLP-UHFFFAOYSA-N Bennol Natural products C1CC(C2)(CO)C=CC32C(O)CC2C(C)(C)CCCC2(C)C31 JHHASXMVMHKBLP-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000191938 Micrococcus luteus Species 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- BGXZJSLTGNPDDH-UHFFFAOYSA-N benzenethiol;sodium Chemical compound [Na].SC1=CC=CC=C1 BGXZJSLTGNPDDH-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229940074355 nitric acid Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000005887 phenylation reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/226—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings
- C07H15/234—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
用な新規化合物である５ 、 ２’， ３’． ４’．
４”、 ６“−ヘキサデオキシカナマイシンおよびそ
の１−Ｎ−（ω一アミノーαーヒドロキシアルカノイル
）−５．２’。DETAILED DESCRIPTION OF THE INVENTION Novel compounds for 5, 2', 3'. 4'.
4", 6"-hexadeoxykanamycin and its 1-N-(ω-mono-α-hydroxyalkanoyl)-5.2'.
５／， ４／， ４１１． ６＃一へキサデオキシカナ
マイシンに関する。5/, 4/, 411. 6#1 Concerning hexadeoxykanamycin.
本発明者らは、アミノ配糖体抗生物質の耐性機構の研究
にもとづいて、カナマイシン群抗生物質の耐性菌に有効
な数多くのデオキシ誘導体を合成した。なかでも、ジベ
カシン（ ３’．４’一ジデメ′キシカナマイシンＢ：
特公昭５０−７５９５号、特許第７９４６１２号、米国
ＩＰｋ ｉｒ ２８３７５３９７３号）は各種の耐性菌
に有効な化学療法剤として、細菌感染症の治療２に広く
用いらノ１．でいる。蜂だ、ハベカシン（１−Ｎ−（（
Ｓ）−４−アミノ−２−ヒドロキシブグリル〕ジベカシ
ン：！庁公昭５２−３３６２９号、米国特許第１１１０
７４２４号）はジベカシン耐性菌にも有効な化学療法剤
として臨床研究が進められている。今回、本発明者らは
、２〃位にたｇ−個の水酸基を残した５ 、 ２’、
３’、 ４’、 ４”、 ６”−ヘギザデオギシカナマ
イシン（以下ヘキサデオキシカナマインンと称す）を合
成し、これがカナマイシンに匹敵する抗菌力をイイする
新規化合物であること、４た、これから更に合成した１
−Ｎ−４（Ｓ）−４−アミノ−２−ヒドロキシブチリル
） −５，２’、３’、４’。The present inventors have synthesized a number of deoxy derivatives effective against bacteria resistant to kanamycin group antibiotics based on research on the resistance mechanism of aminoglycoside antibiotics. Among them, dibekacin (3'.4'1-didemexicanamycin B:
Japanese Patent Publication No. 50-7595, Patent No. 794612, US IPK ir No. 283753973) is widely used in the treatment of bacterial infections as a chemotherapeutic agent effective against various resistant bacteria. I'm here. It's a bee, Habekashin (1-N-((
S)-4-amino-2-hydroxybutryl]dibekacin:! Office Publication No. 52-33629, U.S. Patent No. 1110
No. 7424) is currently undergoing clinical research as a chemotherapeutic agent that is also effective against dibekacin-resistant bacteria. This time, the present inventors left g-hydroxyl groups at the 2-position, 5, 2',
3', 4', 4'', 6''-hexadeoxykanamycin (hereinafter referred to as hexadeoxykanamain) is synthesized and is a new compound with antibacterial activity comparable to that of kanamycin; 4) I synthesized further from this 1
-N-4(S)-4-amino-2-hydroxybutyryl) -5,2', 3', 4'.
４〃７６“−へギーリーデオキシカナマイシン（以下へ
キザデオギシアミカシンと称す）仁［カナマイシン耐性
菌を含めてアミカシンに匹敵する抗菌力を有する新規化
合物であることをそれぞれ確認して本発明を完成した。4〃76''-Hegily deoxykanamycin (hereinafter referred to as hexadeoxyamikacin) did.
本発明の要旨とするところは、新規化合物として、次の
一般式（Ｉ）
〔式中Ａは水素原子または４−アミノ−２−ヒドロキン
ブチリル基を示す〕で表わされる５、２’、３′。The gist of the present invention is to provide, as a new compound, 5,2', 3′.
４／、４ｎ、６“−テトラデオキシカナマイシンまたｋ
ｌ 七の１−Ｎ−アンル誘導体、およびそれらの酸付加
塩にある。4/, 4n, 6"-tetradeoxykanamycin also k
17 1-N-anru derivatives and acid addition salts thereof.
本発明における一般式（Ｉ）の新規化合物の例にケ、１
−１次の化合物が含寸れ、それらの理化学的生物学的性
状は次のとおりである。Examples of the novel compound of general formula (I) in the present invention include:
- It contains the following compounds, and their physicochemical and biological properties are as follows.
（１１ヘキサデオキシ力カーフイシン〔一般式（１）に
おいて八が水素原子の場合〕は、−炭酸塩−水第１ｊ物
の無色粉末と１−で得らｔし、分解点１’９１−１９６
３
′Ｃ１〔α〕 ）１０ろ°（Ｃ１，水）を示した。元素
分析ｌ）
値はＣ４８，９５チ、［１８゜４１％、Ｎ１１゜７１係
を示し、Ｃ＋ＪＩ＊＊ Ｎｑ、Ｏｓ ・Ｉｔ２ （，０
３＠Ｈ２０〕Ｊ’ｌ 論ｆｌｕ （Ｃ４８，７０％。(11 hexadeoxycarboxycin [when 8 is a hydrogen atom in general formula (1)] is obtained by combining colorless powder of -carbonate-water with 1-, and the decomposition point is 1'91-196
3'C1 [α] ) 10 degrees (C1, water). Elemental analysis l) Values show C48,95chi, [18°41%, N11°71, C+JI** Nq, Os ・It2 (,0
3@H20] J'l theory flu (C48, 70%.
Ｊｌ ８．６０％、 Ｎ １１．９６幅）に合致し、マ
ススペクトルでｍ／ｚ’ 、’ｉ８８ （Ｍ＋） ｆ示
した。ノリカゲルの薄層クロマトグラフィーで、ブタノ
ール・エタノール・クロロホルム・１７％アンモニア水
（４：５：２：５Ｗ）およびクロロホルムφメタノール
−ａアンモニア水・水（１：４：２：１芥）の混液を展
開溶媒として、それぞれＲｆ ０６４７および０．７８
に単一スポットにンヒドリン発色）を示した。Jl 8.60%, N 11.96 width), and the mass spectrum showed m/z' and 'i88 (M+) f. Using Norica gel thin layer chromatography, a mixture of butanol, ethanol, chloroform, 17% aqueous ammonia (4:5:2:5W) and chloroformφmethanol-a aqueous ammonia and water (1:4:2:1) was prepared. Rf 0647 and 0.78 as developing solvents, respectively.
showed nhydrin color development in a single spot.
抗菌スはクトルは第１辰に示］−だ。Antibacterial agents are shown in the first column.
（２） へギザデＡキシアミカシン〔一般式（Ｉ）に
おいてＡが（Ｓ） −４−アミノ−２−ヒドロキンブチ
リル基−ＣＯＣＩｔ（ＯＩＩ）（ＪＴ２ＣＪｒ２Ｎｌ’
ｉ２の場合〕は、−炭酸塩二水和物の無色粉末として得
られ、分解点１５７−１６２℃、〔αＪ、、 ＋６１”
（ｃｌ 、水）を示した。元素分析値ｕ：ｃ４７．１
６％、 Ｉｔ ８．１ろチ、 Ｎ １１．６１％を示し
、Ｃ２，Ｉｔ４３Ｎ、Ｏ，・Ｔ１２Ｃｏ、・２Ｈ，Ｏの
哩論値（Ｃ４７゜０１％。(2) Hegizade A xamikacin [in general formula (I), A is (S) -4-amino-2-hydroquine butyryl group -COCIt(OII) (JT2CJr2Nl'
i2] is obtained as a colorless powder of -carbonate dihydrate, with a decomposition point of 157-162°C, [αJ,, +61''
(cl, water) was shown. Elemental analysis value u: c47.1
6%, It 8.1%, N 11.61%, and the theoretical value of C2, It43N, O, ・T12Co, ・2H, O (C47°01%.
Ｈ８，４０％、 Ｎ １１．９２％ ）に合致し、マス
スペクトルでＭ＋を観測できなかったが、ＮＭＲスはク
トルで、その構造が支持された。シリカケ゛ルの薄層り
１７マトグラフイーで、ブタノール・エタノール・クロ
ロホルム・１７％７ンモー＝−ア水（４： ５ ： ２
：５容）およびクロロホルム・メタノール・濃アンモニ
ア水・水（１：４：２：１容）の混液を展開溶媒として
、それぞれＲｆ ０．３１および０．４６に中−スポッ
トを示しだ。抗菌スばクトルは第１衣に示した。(H8, 40%, N 11.92%), and although M+ could not be observed in the mass spectrum, the NMR spectra were ctoles, supporting the structure. A thin layer of silica cell 17 chromatography was used to prepare butanol, ethanol, chloroform, 17% 7% aqueous water (4:5:2).
Using a mixture of chloroform/methanol/concentrated ammonia/water (1:4:2:1 volume) as a developing solvent, medium spots were shown at Rf 0.31 and 0.46, respectively. Antibacterial bacteria are shown in the first coat.
第 １ 衣
ミクロコツカス・ルテウスＰＣ１１００１１２，５７５
，２５（第１表つづき）
本発明で得られた新規化合物は通常遊離塩基または水和
物または炭酸塩として得られるが、通常の方法により薬
学的に許容できる酸を加えて任意の無毒性の酸付加塩と
することができるっ付ＪＪＨ’ｒべき酸としては塩酸、
臭化水累晒、ｆｆ＋ｆ酸、川ｔＳ：Ｘ 。1st Cloth Micrococcus luteus PC1100112,575
, 25 (Continued from Table 1) The novel compounds obtained in the present invention are usually obtained as free bases, hydrates or carbonates, and can be prepared by adding a pharmaceutically acceptable acid to any non-toxic compound by a conventional method. Examples of acids that can be made into acid addition salts include hydrochloric acid,
Accumulated bromide exposure, ff+f acid, river tS:X.
硝酸などの無４幾１亥、リンゴ酸、クエン酸、アスコル
ビン酸、メタンスルホン酸などの有機酸が用いられる。Organic acids such as nitric acid, malic acid, citric acid, ascorbic acid, and methanesulfonic acid are used.
本発明における新規化合物は、本発明者らによって合成
されたｓｌ、４１−ジデオキシカナマイシン（特願昭５
４−１１４０２号；特開昭５５−１０５６９９号明細＠
参照）を出発原料として合成することができる。The novel compound of the present invention is sl,41-dideoxykanamycin (Japanese Patent Application
No. 4-11402; JP-A No. 55-105699 @
(see ) can be synthesized using as a starting material.
一般式（ＩＩ） 〔式中、Ｒは水素原゛子を示す〕で表ゎさ丸る６′。General formula (II) [In the formula, R represents a hydrogen atom] is a rounded 6'.
４′−ジデオギシカナマイシンの４個のアミン基を、常
法により、アミノ保に＠基で保護ｊ−た化合物〔一般式
（１１）において、籠がウレタン型のアミン保護基（ｎ
Ｏｃ＝ｏ）になった場合、但しＢけアルキル、ンクロア
ルキル又はアラルキル基を示す〕とし、続いて無水溶液
中水素化ナトリウムなどの塩基で公知方法で処理して２
ｔｒ、ｙ位に環状カルノコメートを形成させ、次の一般
式（１！ｌ）
１ １ノ
〔式中、Ｐ、は前述と回じアミノ保護基でありＳ Ｒ’
Ｉｎ２は水酸基である〕で表わされる化合物とし、次
にこれを塩化トリフロロメタンスルホニルと反応させて
、２’、４”および６〃位の水酸基（Ｒ１）をスルボン
酸エステル化シ、続いてスルホン酸エステル基をテオフ
エへ−ルナトリウムでチオフェニル化し、さらに加水素
分解して、デオキシ化合物〔一般式（１）において、Ｒ
は前述と同じアミン保護基であり、Ｒ１は水素原子にな
り、Ｒ２は水酸基である場合〕を得、次に二硫化炭素、
水酸化ナトリウムおよびヨウ化メチルの反応′にょって
５位の水酸基をＳ−メチルジテオカルボニル化し、続い
て加水分解して５−デオキシ化合物〔一般式（１）にお
いて、Ｒは前述と同じアミン保護基であり、Ｒ１、Ｒ２
は水素原子になつ′Ｐｃｓ合〕とし、終りに２種のアミ
ン保護基を脱離して、一般式（Ｉａ）
で衣わされるヘキサデオキシアミカシンを製造すること
がでべろ。A compound in which the four amine groups of 4'-dideogishikanamycin were protected with @ groups on the amino group by a conventional method [in general formula (11), the cage was a urethane-type amine protecting group (n
Oc=o), provided that B represents an alkyl, cycloalkyl, or aralkyl group], and then treated with a base such as sodium hydride in an anhydrous solution by a known method to obtain 2.
A cyclic carnocomate is formed at the tr and y positions, and the following general formula (1!l) 1 1 [wherein, P is an amino protecting group as described above and S R'
In2 is a hydroxyl group], and this is then reacted with trifluoromethanesulfonyl chloride to convert the hydroxyl groups (R1) at the 2', 4'' and 6th positions into sulfonic acid esters, followed by sulfonic acid esterification. The acid ester group is thiophenylated with sodium theophele and further hydrolyzed to form a deoxy compound [in general formula (1), R
is the same amine protecting group as above, R1 is a hydrogen atom, and R2 is a hydroxyl group], then carbon disulfide,
The hydroxyl group at the 5-position is S-methyl ditheocarbonylated by the reaction of sodium hydroxide and methyl iodide, and then hydrolyzed to form a 5-deoxy compound [In general formula (1), R is the same amine as above. Protecting group, R1, R2
is converted into a hydrogen atom by 'Pcs combination], and finally the two amine protecting groups are removed to produce hexadeoxyamikacin represented by the general formula (Ia).
本発明におけるヘキサデオキシアミカシン〔一般式（Ｉ
［）においてＡが（Ｓ） −４−アミノ−２−ヒドロキ
シブチリル基（Ｈ，ＮＣ１１２ＣＩＩ、Ｃ１１（ＯＨ）
Ｃｏ）である場合〕５Ｃ製造するに当っては、既知の種
々の１−Ｎ−アシル化方法によって、ヘキサデオキシア
ミカシン〔一般式（Ｉ）においてＡが水素原子の場合〕
の１位のアミノ基を（Ｓ） −４−アミノ−２−ヒドロ
キシ醋酸又はその反応性誘導体又はそのＮ−保役体でア
シル化することによって達成されるが、本発明者らによ
る６、６′お上びろ〃位の７′ミノ基の選択的保護法（
特願昭５３−１３８４０２号、特願昭５４−７６０６４
号、特願昭５６−５８３８９号）によってヘキサデオキ
シアミカシンの１位以外のアミノ基を保護された保護誘
導体を作り、これから１−Ｎ−アシル誘導体を製造する
方法が最も有用な方法である。Hexadeoxyamikacin in the present invention [general formula (I
In [), A is (S) -4-amino-2-hydroxybutyryl group (H, NC112CII, C11(OH)
[When A is a hydrogen atom in general formula (I)] In producing 5C, hexadeoxyamikacin [when A is a hydrogen atom in general formula (I)] is produced by various known 1-N-acylation methods.
This is achieved by acylating the amino group at the 1-position of (S)-4-amino-2-hydroxyacetic acid or its reactive derivative or its N-support body, which is achieved by the present inventors' 6,6 Selective protection method for the 7′ mino group at the top and bottom positions (
Patent Application No. 138402/1982, Patent Application No. 76064/1983
The most useful method is to prepare a protected derivative of hexadeoxyamikacin in which amino groups other than the 1-position are protected, and to produce a 1-N-acyl derivative from the protected derivative according to Japanese Patent Application No. 56-58389.
次に実施例によって、本発明の化合物の製造法を説明す
る。Next, the method for producing the compound of the present invention will be explained with reference to Examples.
実施例１
ヘキサデオキシカナマインンの合成：
（イ） ６′、４′−ジデオキシカナマインン１゜２０
．９（２，６５ミリモル）に、水２０ ｍ１１メタ／−
ル２Ｄｍｌ、トリエチルアミ：／１７ｍ１（１２，２ミ
リモル）を加えて溶解し、ベンジル−４，６−ヅメナル
ビリミド−２−イルチオカルボネート５．０３ ｇ（１
８，４ミリモル）を２０ｍのメタノールにとかした溶液
を加え、室温で２４時間攪拌してアミノ保護反応を行っ
た。反応液に１７チアンモニア水０゜５ｍｌを加え、濃
縮乾固した。残渣を水５Ｑｍｌで２回、ｎ−ヘキサン３
［１ｍで１回洗浄し、１，３．（Ｓ’、３’−テトラキ
ス−Ｎ−ベンジルカルボニル−３’、 ４”；デオキシ
カナマイシンの無色粉末２．３０ 、！ｉ’を得た（収
率７９チ）。Example 1 Synthesis of hexadeoxykanamain: (a) 6',4'-dideoxykanamain 1°20
．． 9 (2,65 mmol) to 20 ml of water /-
Add and dissolve 2 Dml of triethylamine, 17 ml (12.2 mmol) of triethylamine, and dissolve 5.03 g (1
A solution of 8.4 mmol) dissolved in 20 m of methanol was added, and the mixture was stirred at room temperature for 24 hours to carry out an amino protection reaction. 0.5 ml of 17-thiammonia water was added to the reaction solution, and the mixture was concentrated to dryness. The residue was diluted with 5 Qml of water twice and 3 times with n-hexane.
[Wash once at 1 m, 1, 3. (S', 3'-tetrakis-N-benzylcarbonyl-3', 4''; colorless powder of deoxykanamycin 2.30,!i' was obtained (yield: 79 cm).
（ロ） 前項（イ）で得られた１、３．６’、３ｇ−テ
トラギスーＮ−（ンジルカルボニルー３’、４’−ジデ
オキシカナマイシン２．２０９（２，０１ミリモル）を
無水Ｎ。(b) 2.209 (2.01 mmol) of 1,3.6',3g-tetragys-N-(ndylcarbonyl-3',4'-dideoxykanamycin) obtained in the previous section (a) was mixed with anhydrous N.
Ｎ−ジメチルホルムアミド７Ｑｍｌにとかし、アルゴン
気流下６０チ水素化ナトリウム８ ｏ ４ ｍｇ （２
［］、１ミ１ミリ）を加え、室温で３時間攪拌した（２
〃。Dissolve in 7 Q ml of N-dimethylformamide, add 8 o 4 mg (2
[ ], 1 mm 1 mm) was added and stirred at room temperature for 3 hours (2
〃.
ろ“−環状力ルバメート体の生成）。反応液に酢酸１．
２ｍ１２０゜１ミリモル）を加え、濃縮乾固した。(Production of cyclic albamate compound). Add 1.0% acetic acid to the reaction solution.
2ml 120° 1 mmol) was added and concentrated to dryness.
残渣を２００ｍ１の水で洗浄し、１，３ 、６’−トリ
ス−Ｎ−ベンジルオキシカルボニル−３’、４’ −’
；デオキシカナマイシンー２ｎ、ｘ、ｔｒ−カルバメー
トの無色粉末ｔｉｏｇを得た（収率６２チ）。分解点２
２１−２２６℃、〔α〕ｏ＋６７°（ｃｌ、Ｎ、Ｎ−ジ
メチルホルムアミド）。元素分析値： Ｃ５８，８４％
。The residue was washed with 200 ml of water and 1,3,6'-tris-N-benzyloxycarbonyl-3',4'-'
A colorless powder tiog of deoxykanamycin-2n,x,tr-carbamate was obtained (yield: 62cm). Decomposition point 2
21-226°C, [α]o+67° (cl, N, N-dimethylformamide). Elemental analysis value: C58,84%
.
Ｈ５，６３％、 Ｎ ６．３１％。Ｃ４３Ｈ５２Ｎ４０
１６の理論値：Ｃ５８，６３チ、 Ｈ５，９５％、 Ｎ
６．５６％。H5, 63%, N 6.31%. C43H52N40
Theoretical value of 16: C58, 63chi, H5, 95%, N
6.56%.
（ハ） 前項（ロ）で得られた１、３．６’−１リス−
Ｎ−ベンジルオキシカルボニル−５’＋４’−’）デオ
キシカナマイシン−７１，３Ｎ−カルバメート１．０５
ｇを無水ピリジン８０ｍ１にとかし、４−ジメナルアミ
ノビリジン４３６ｍ９（３，５７ミリモル）を加えた溶
ＨＫ 、 水冷上塩化トリフロロメタンスルホニル１．
１４ｍｌ （１０，２ミリモル）を滴加し、続いて室温
で２時間攪拌した（水酸基のスルホン酸エステル化）。(c) 1,3.6'-1 lithium obtained in the previous section (b)
N-benzyloxycarbonyl-5'+4'-')deoxykanamycin-71,3N-carbamate 1.05
1.g of trifluoromethanesulfonyl chloride was dissolved in 80 ml of anhydrous pyridine, 436 m9 (3,57 mmol) of 4-dimenalaminopyridine was added, and trifluoromethanesulfonyl chloride was cooled with water.
14 ml (10.2 mmol) was added dropwise, followed by stirring at room temperature for 2 hours (sulfonate esterification of hydroxyl groups).
反応液に水ｉ ｍｌを加えて濃縮し、残渣を５Ｑ＋＋＋
ｌの酢酸エテルに溶解し、飽和炭酸水素ナトリウム水溶
液５Ｑｍ、水５Ｑｍｌで洗浄したのち、酢酸エチル層を
無水硫酸すｉ ＩＪウムで脱水し−Ｃａ縮乾固した。残
渣をシリカゲル（和光紬薬：ワコーゲルＣ−２００，１
００ｇ）のカラムクロマトグラフィー（クロロホルム−
メタノール、６０：１で展開、２０ｄ分画）で精製し、
分画４７−６１を合し、濃縮乾固して１，３．６’−ト
リス−Ｎ−インジルオキシカルボニル−２７，４＃ 、
６Ｎ −トリス０− ） ＩＪフロロメタンスルホニ
ル−３７，４／−ジテオキシカナマイシン−２ｔｔ、ｙ
−カル／２メート６２３〜を得た（収率４１％）。Add 1 ml of water to the reaction solution, concentrate, and convert the residue to 5Q+++
After washing with 5 Qml of a saturated aqueous sodium bicarbonate solution and 5Qml of water, the ethyl acetate layer was dehydrated with anhydrous sodium sulfate and -Ca condensed to dryness. The residue was treated with silica gel (Wako Tsumugi: Wakogel C-200,1
00g) column chromatography (chloroform-
Developed with methanol, 60:1, purified with 20d fraction),
Fractions 47-61 were combined and concentrated to dryness to give 1,3,6'-tris-N-indyloxycarbonyl-27,4#,
6N-Tris0-) IJ fluoromethanesulfonyl-37,4/-diteoxykanamycin-2tt,y
-Cal/2mate 623~ was obtained (yield 41%).
に） 前項（ハ）で得られた１、３．６’−１リス−Ｎ
−ベンジルオキシカルボニル−２’、４’、６“−トリ
ス−Ｏ−） ＩＪフロロメタンスルホニル−３’、４’
−ジデオキシカナマイシン−２＃、！、＃−カルバメー
ト６２０ｍ９Ｃ０，４８５ミリモル）を無水Ｎ、Ｎ−ジ
メチルホルムアミド７０ｍ１にとかし、チオフェノール
ナトリウム３８５ｒｎｙ（２，９１ミリモル）を加え、
室温で２時間攪拌した（チオフェニル化）。) 1,3.6'-1 Lis-N obtained in the previous section (c)
-benzyloxycarbonyl-2',4',6"-tris-O-) IJ fluoromethanesulfonyl-3',4'
-Dideoxykanamycin-2#,! , #-carbamate (620 m9C0,485 mmol) was dissolved in 70 m1 of anhydrous N,N-dimethylformamide, 385 rny (2,91 mmol) of sodium thiophenol was added,
Stirred at room temperature for 2 hours (thiophenylation).
反応液を濃縮乾固し、残渣を酢酸エチル７．０ｍ１ＶＣ
とかし、水３Ｑｍｌで２回洗浄したのち、酢酸エチル層
を無水硫１′官ナトリウムで脱水して濃縮乾固した。、
残渣をシリカゲル（ワコーゲル、Ｃ−２００，７０ｇ）
のカラムクロマトグラフィー（クロロホルム−メタノー
ル、６ ［１： １で展開、１４ｍｇ分画）で精製し、
分画３６−５！ｌを合し、濃縮乾固して、１．３．６’
−）リス−Ｎ−＜ンジルオキシカルボニル−１、４”、
６”−）リスチオフェニル−ｓｌ、４／−ジブ′第４
゛シカナマイシン−２“、３〃−カルノぐメート４１５
ｍ９を得だ（収率７４多）。The reaction solution was concentrated to dryness, and the residue was dissolved in 7.0 ml of ethyl acetate (1VC).
After stirring and washing twice with 3Qml of water, the ethyl acetate layer was dehydrated over anhydrous sodium sulfate and concentrated to dryness. ,
Pour the residue into silica gel (Wakogel, C-200, 70g)
Purified by column chromatography (chloroform-methanol, developed with 6 [1:1, 14 mg fraction),
Fraction 36-5! 1.3.6' was combined and concentrated to dryness.
-) Lis-N-<ndyloxycarbonyl-1,4",
6”-) listhiophenyl-sl, 4/-dibu′4th
“Cicanamycin-2”, 3-Carnogumate 415
m9 was obtained (yield 74%).
（ホ） 前項に）で得られた１、５．６’−トリス−Ｎ
−ベンジルオキシカルボニル−２’、 ４”、 ６’−
トリスチオフェニル−３／ 、 、ｓｌ−ジデオキシカ
ナマイシン−２“、３〃−カルバメート４１１ｍ９（０
，３５５ミリモル）をエタノール５Ｑ＋＋＋Ａ！にとか
し、ラネーニッケル（日興理化学産業ｇ−２ｏｏ）ｈ加
えて、９０゛℃で２時間還流して加水素分解を行った。(e) 1,5.6'-Tris-N obtained in the previous section)
-benzyloxycarbonyl-2', 4'', 6'-
Tristhiophenyl-3/, , sl-dideoxykanamycin-2'', 3〃-carbamate 411m9 (0
, 355 mmol) in ethanol 5Q+++A! Then, Raney nickel (Nikko Rikagaku Sangyo G-2OO) was added thereto, and the mixture was refluxed at 90°C for 2 hours to perform hydrolysis.
触媒を除去し、濃縮乾固したのち、シリカゲル（ワコー
ケ゛ルＣ−２ｆＪ ０１５０ｇ）のカラムクロマトグラ
フィー（クロロポルム−メタノール、５０：１で展開、
ｊＯｍ１分画）で精製し、分画５ろ一７６金合して濃縮
乾固し、１，３．６’−トリス−Ｎ−ベンジルオキシカ
ルボニル−２′、３／、 ４Ｎ、 ６１１− ペンタデ
オキシカナマイシン−２“、３“−カル／２メート２１
３ｍ９を得た（収率７２チ）。 ゛
（へ） 前項（ホ）で得られた１、３．６’−）リス−
Ｎ−カルジルオキシ力ルボニル−２／ 、 ３／ 、
４／ 、 ４／ｆ 、 ６／／−ペンタデオキシカナマ
イシン−２“、３〃−カルパメー）２０９ｍｆｔ’（０
，２５１ミリモル）をジメグルスルホキシド２ ｍｌに
とかし、二硫化炭素Ｃ３，１５ｍｌ （２，５１ミリモ
ル）を加え、水冷下５Ｎ水酸化す） ＋７ウノ、０．２
５ｍ１ｌ（１，２５ミリモル）を滴加し、続いてろ０分
間攪拌した。反応液にヨウ化メチルＤ、１．’１ｍｅｄ
を加え、酢酸エテル２（Ｊｍｌで２回抽出した。抽出液
を無水硫酸ナトリウムで脱水し、濃縮乾固したのち、シ
リカゲル（ワコーゲルＣ−２００，２０ｇ）のカラムク
ロマトグラフィー（クロロホルム−メタノール、８０：
１で展開、４ ｍ１分画）で精製し、分画４７−６２を
合（７て濃縮乾固し、１゜３１６’−トＩＪスーＮ−ペ
ンジルオキン力ルボニル−２’、３’、４’、４“、６
“−はンタデオキシー５−Ｏ−（Ｓ−メナルジチオ力ル
ボニル）カナマイシン−２“。After removing the catalyst and concentrating to dryness, column chromatography on silica gel (Wako Kel C-2fJ 0150g) was performed (developed with chloroporm-methanol, 50:1).
1,3,6'-tris-N-benzyloxycarbonyl-2',3/,4N,611-pentadeoxy Kanamycin-2", 3"-cal/2mate 21
3m9 was obtained (yield: 72cm).゛(f) 1,3.6'-)ris obtained in the previous section (e)
N-cardyloxycarbonyl-2/, 3/,
4/, 4/f, 6//-pentadeoxykanamycin-2'', 3〃-carpame) 209 mft' (0
, 251 mmol) was dissolved in 2 ml of dimegyl sulfoxide, 15 ml (2,51 mmol) of carbon disulfide C was added, and the mixture was hydroxylated with 5N under water cooling.
5 ml (1.25 mmol) were added dropwise, followed by stirring for 0 minutes. Add methyl iodide D to the reaction solution, 1. '1med
was added and extracted twice with ethyl acetate 2 (Jml). The extract was dehydrated with anhydrous sodium sulfate, concentrated to dryness, and then subjected to column chromatography on silica gel (Wako Gel C-200, 20 g) (chloroform-methanol, 80:
The fractions 47-62 were combined (7 and concentrated to dryness, yielding 1°316'-toIJ-N-pendzyl-2', 3', 4'). ,4",6
"-antadeoxy-5-O-(S-menaldithiocarbonyl)kanamycin-2".
ろ“−カル・ごメート１６５ｍ９を得た（収率７１％）
。Obtained 165m9 of Ro'-Cal Gomate (yield 71%)
.
（ト） 前項（へ）で１丘ら力、た１ 、 ３ 、６
’−トリス−Ｎ−ベンジルオキシカルボニル−２’、
３’、 ４’、 ４“、６〃−はンタデオキシー５−Ｏ
−（Ｓ−メチル−ジテオカルボニル）カナマイシン−２
“、３〃−カルバメート１６２ｍｆｌ（０，１７６ミリ
モル）を無水トルエン５ｍｌにとかし、α、α′−アゾ
ビスイソブチロニトリル５１ηノとトリグナルスタナン
１ ｍｌを加え、アルゴン気流下、８０ ’Ｃに加熱し
て攪けし′／？Ｌ（加水累分解）。反応液を濃縮乾固１
−たのぢ、シリカゲル（ワコーゲルＣ−２００，２０，
９）のカラムクロマトグラフィー（クロロホルム−メタ
ノール、５０：１で展開、４ ｍ１分画）で蒋製し、分
画３７−４９を合（７て濃縮乾燥し＋ １ ｇ Ｊ
＋ ６’−トリス−Ｎ−ベンジルオキシカルボニル−５
、２’、ろ／、４１．４“、６”−ヘキサデオキシヵナ
マイシン−７，６〃−カル７２メ・−）１１２ｇを得た
（収率７８％）。(g) In the previous section (f), 1 hill force, ta 1, 3, 6
'-tris-N-benzyloxycarbonyl-2',
3', 4', 4", 6-antadeoxy-5-O
-(S-methyl-diteocarbonyl)kanamycin-2
162 mfl (0,176 mmol) of 3-carbamate was dissolved in 5 ml of anhydrous toluene, 51 η of α,α'-azobisisobutyronitrile and 1 ml of trignalstanane were added, and the mixture was heated at 80'C under an argon atmosphere. Heat to 1/2L and stir (hydrolysis). Concentrate the reaction solution to dryness.
-Tanoji, silica gel (Wakogel C-200, 20,
9) column chromatography (developed with chloroform-methanol, 50:1, 4 ml fractions), and fractions 37-49 were combined (7) and concentrated and dried to yield + 1 g J
+ 6'-tris-N-benzyloxycarbonyl-5
, 2', ro/, 41.4", 6"-hexadeoxykanamycin-7,6〃-cal72me-) was obtained (112 g, yield 78%).
０う 前項（ト）で得られた１ 、ろ、６’−）リス−
Ｎ−ベンジルオキシカルボニル−５、２’、 ３’、
４’、 ４“、６“−へキサデオキシカナマイシン−２
″、ろ〃−カルノぐメート１０８ｍ１？（０，１３２ミ
リモル）ｉ９Ｊキザン５ ｍｌにとかし、０．１Ｎ水酸
化バリウム６ ｍｌを加えて、６０℃１時間加温攪拌し
た。反応液を固型炭酸で中和し、沈澱を戸去した。Ｅ液
に５チパラジウム一炭素１０ｍ９を加え、水素気流中で
６時間室温で攪拌した（アミン保護基の脱離）。触媒を
除去し、Ｅ液をアンバーライトＣＧ −５０ｆ何脂（Ｎ
ｌｌ、” ）１Ｑｍｌのカラムにかけて、生成物を吸着
せしめ、水ろＯｍｅおよび０．１Ｎアンモニア水３０ｍ
ｅで洗浄後、０．６Ｎアンモニア水で溶出した（ ｉ
ｍｅ分画）。0 U 1 obtained in the previous section (g), ro, 6'-)lis-
N-benzyloxycarbonyl-5, 2', 3',
4', 4", 6"-hexadeoxykanamycin-2
108 ml of ro-carnogumate (0,132 mmol) was dissolved in 5 ml of i9J Kizan, 6 ml of 0.1N barium hydroxide was added, and the mixture was heated and stirred at 60°C for 1 hour.The reaction solution was dissolved in solid carbonate. and the precipitate was removed. 10 m9 of 5-thipalladium-carbon was added to solution E, and the mixture was stirred at room temperature for 6 hours in a hydrogen stream (elimination of the amine protecting group). The catalyst was removed, and solution E was Amberlight CG -50f fat (N
ll,”) 1Qml column to adsorb the product, water filter Ome and 0.1N ammonia water 30ml
After washing with e, it was eluted with 0.6N ammonia water (i
me fraction).
分画６−８を合して濃縮乾固し、ヘキナデオギンカナマ
イシンの無色粉末（−炭酸塩−水和物）４６ｍｇを得た
（収率７４％）。Fractions 6-8 were combined and concentrated to dryness to obtain 46 mg of colorless powder (-carbonate-hydrate) of hequinadeogin kanamycin (yield: 74%).
実施例２
ヘキザデオキシアミ力シンの合成：
（イ） 実施例１で得られたヘキサデオキシカッ−マイ
’／ ン４０ ｍ９ （ＩＴ、［Ｉ ８５ミリモル）’
ｔ ９０％ジメテルスルホギシ）パ水溶’ｌ（＋ ｓ
ｍｅにとかし、酢酸１１１ｊ ｊｆｌ［Ｚｎ（ＯΔｃ）
２ − ２Ｈ７（１，） １０９ １η９（０，／１
９４ ミ リ モ ル ）を加え、室温で１５時間攪
拌したのち、ベンジル−４，６−ジメチールビリミド−
２−イルチオカルボネート１１０ｍｇ（ｌＪ、４０２ミ
リモル）を加え、５０′Ｃに加温して７時間攪拌した（
アミン保護基の導入反応）。反応液にエーテル５ｏｍｌ
を加えて生成物を沈澱させたつこれをシリカゲル（ワコ
ーゲルＣ−２００％ ２ ｒｌ 、ｑ）のカラムクロマ
トグラフィー（クロＴｆｆホルムーメタノールー濃アン
モニア水、２０ ： １０ ： １−？ｌ’展開、４ｍ
１分両）テ梢製し１分画３ｌ−４０ｆＸ：合して濃縮乾
固し、３，６゜５“−トリス−Ｎ−ベンジルオキシカル
ボニルへキサデオキシカナマイシン４１ ｍ９を得た（
収率６１チ）。Example 2 Synthesis of hexadeoxyamylicin: (a) Hexadeoxykamine obtained in Example 1 40 m9 (IT, [I 85 mmol)'
t 90% dimethyl sulfogycin) water soluble'l (+s
me and acetic acid 111j jfl[Zn(OΔc)
2 − 2H7(1,) 109 1η9(0,/1
After stirring at room temperature for 15 hours, benzyl-4,6-dimethylpyrimide-
110 mg (lJ, 402 mmol) of 2-ylthiocarbonate was added, heated to 50'C and stirred for 7 hours (
amine protecting group introduction reaction). Add 5 ml of ether to the reaction solution.
was added to precipitate the product, which was then subjected to column chromatography on silica gel (Wako Gel C-200% 2 rl, q) (chromatography form-methanol-concentrated aqueous ammonia, 20:10:1-?l' development, 4 m
The fractions 3l-40fX were combined and concentrated to dryness to give 41 m9 of 3,6゜5"-tris-N-benzyloxycarbonylhexadeoxykanamycin (
Yield: 61 cm).
（ロ） 凸ｉ１ 項（イ）で 得 ら 、Ｉｔ／仁
３ 、 ６ 、 ３” −ト リ ス −
Ｎ −ベンジルオキ７カルポニルへキサデオキシカナマ
イシン３５Ｉｎ９（０，０４４ミリモル）をジメチルス
ルホキシド５ｍ／！にとか１７、トリエチルアミン０．
０１ｍ１（０，０６６ミリモル）と（Ｓ） −４−ヘｙ
シルオキシカルボニルアミノ−２−ヒドロギン酪ｒ１
マのＮ−ヒドロキンコハク酸イミドエステル２２〜（ｎ
、０６６ミリモル）をテトラヒドロフラン１ｍｌにとか
した溶液を加え、室温で４時間攪拌した（１−Ｎ−アシ
ル化反応）。反応液に水５Ｑｍｌを加え、酸１ｐ′Ｔ−
チル３［］ｍｇで２回抽出した。抽出液を無水硫酸−ノ
ートリウムで脱水（７、濃縮乾固１〜ブこのち、ンリカ
ク゛ル（ワコーゲルＣ−２００，１０ｇ）のカラムクロ
マトグラフィー（クロロホルム−メタノール、１０：１
で展開、２ｍ１分画）で’Ａ７ｆ製（−１分画３７−４
４を合して濃縮乾固し、ろ、６．ろ〃、４ｍ−デトラキ
スーＮ−ペンジルオキン力ルポニルへキザデオキシアミ
力シン３４ｍｇを得た（収率７６％）。(b) Obtained by the convex i1 term (a), It/ren 3, 6, 3" - Tris -
N-benzylox7carponylhexadeoxykanamycin 35In9 (0,044 mmol) was mixed with dimethyl sulfoxide 5m/! Toka 17, triethylamine 0.
01m1 (0,066 mmol) and (S)-4-hay
Syloxycarbonylamino-2-hydrogine butyro r1
N-hydroquine succinimide ester 22~(n
, 066 mmol) dissolved in 1 ml of tetrahydrofuran was added thereto, and the mixture was stirred at room temperature for 4 hours (1-N-acylation reaction). Add 5Qml of water to the reaction solution and add 1p'T- of acid.
Extracted twice with 3 [] mg of chill. The extract was dehydrated with anhydrous sulfuric acid and sodium chloride (7), concentrated to dryness, and then subjected to column chromatography (chloroform-methanol, 10:1
Developed with 2m1 fraction) and 'A7f (-1 fraction 37-4
Combine 4 and concentrate to dryness, filter, 6. 34 mg of 4m-detrakis-N-pendyloxyaminochloride was obtained (yield 76%).
（ハ） 前項（ロ）で得られた３、６．３”、４″′−
デトラギスーＮ−ベンジルオキシカルボニルへキザデ゛
オキノアミ力シンろ３”９（０，０６ろミリモル） ｆ
５ ［１％メタノール水５ ｍｌと酢酸０．０１ｍ／
の混液にとかし、５％パラジウム炭素３ ｍ９を加え、
水素気γＭｆ、中室温で７時間攪拌した（脱保護反応）
。ｆφ１！四を除去１−５濃縮乾固したのち、残渣を５
−の水にとがし、アンバーライトＣＧ−５Ｑ樹脂（ＮＨ
：）５罰のカラムに通して生成物を吸着させた。水１５
ｄおよび０．２Ｎ７７％＝ア水で洗浄後、０．５Ｎアン
モニア水で溶出した（０．５ＴＬ１分画）。分画８−１
３を合して濃縮乾固し、ヘキサデオキシアミカシンの無
色粉末（−炭阪塩二水和物）１３雫を得た（収率６７％
）。(c) 3, 6.3", 4"'- obtained in the previous section (b)
Detragis-N-benzyloxycarbonyl hexadecyloxycarbonyl 3"9 (0.06 mmol) f
5 [5 ml of 1% methanol water and 0.01 m of acetic acid/
Dissolve the mixture, add 3 m9 of 5% palladium on carbon,
Stirred in hydrogen gas γMf at room temperature for 7 hours (deprotection reaction)
. fφ1! After removing 1-5 and concentrating to dryness, the residue was reduced to 5
- Sharpen in water, Amberlite CG-5Q resin (NH
:) The product was adsorbed through a 5-particle column. water 15
After washing with d and 0.2N 77% aqueous water, it was eluted with 0.5N ammonia water (0.5TL1 fraction). Fraction 8-1
3 were combined and concentrated to dryness to obtain 13 drops of colorless powder of hexadeoxyamikacin (-Kanzanhan salt dihydrate) (yield 67%).
).
手続補正書（自発）
昭和５８年１２月２０ｆＥ
特許庁長官殿
■、小事件表示
昭和５７ 年特許願第１６２２９２号２、発明の名称
３、補正をする者
事件との関係 ％ｔ〕出願人
住 所 東京部品用区上大崎３丁目１４番２３号名
称 財団法人 微生物化学研発会４、代理 人
〒１０５ 住所 東京都港区西新橋１丁］」１番１５
号物産ビル別館 電話（５９１） ０２６１よ補正の対
象
明細書の特許請求の範囲の欄及び発明の詳細な説明の欄
を補正の内容
（１）特許請求の範囲を別紙のとおり補正する。Procedural amendment (spontaneous) December 20th, 1980 Mr. Commissioner of the Japan Patent Office■, Small case indication Patent Application No. 162292 of 19822, Title of invention 3, Relationship with the case of the person making the amendment %t] Applicant's residence Address: 3-14-23 Kamiosaki, Tokyo Parts Ward
Name: Microbial Chemistry Research Foundation 4, Agent Address: 1-15 Nishi-Shinbashi 1-chome, Minato-ku, Tokyo 105
Bussan Building Annex Tel: (591) 0261 Contents of the amendment: (1) The scope of claims will be amended as shown in the attached sheet.
（，２）明細書第グ頁ｊ行の「テトラ」を削除して「ヘ
キサ」を挿入する。(,2) Delete "tetra" and insert "hexa" in line j of page G of the specification.
（３〕 同第１頁表中３行のｒＦＬ／３！ＪをｒＲ／
３ｊＪと補正する。(3) Change rFL/3!J in row 3 in the table on the first page to rR/
Correct it as 3jJ.
（４’） 同第ｉｏ頁３行の「リンゴ」の前に「酢酸
、」を挿入する。(4') Insert "acetic acid," before "apple" in line 3 of page io.
（ｔ）同第１．２頁μ行の「チオフェノール」の次に「
酸」を挿入する。(t) Next to “thiophenol” on page 1.2, line μ, “
Insert "acid".
（＆） 同第１コ頁グ行の［フェニル化ｊの次にｒ
（−８Ｃ６Ｈ５基による置換）」を挿入する。(&) On the first co-page line, [phenylation j is followed by r
(substitution with -8C6H5 group)" is inserted.
（７）同第１．２頁１０行の「続いて加水分解」を削除
して［すなわち５位の基を基−０−０（＝Ｓ）−８−Ｏ
Ｈ３に転化し、続いて加水素分解」を挿入する。(7) Delete "subsequently hydrolyzed" in line 10 of page 1.2 [i.e., the group at position 5 is replaced with -0-0(=S)-8-O
H3 followed by hydrolysis.
＜ｒ）同第７．２頁／３行の「終りに」の次に［ウレタ
ン型及びカルノ々メート型の」を挿入する。<r) Insert "Urethane type and carnomate type" after "At the end" on page 7.2/line 3.
（り） 同第７２頁ｌ１行の「一般」を削除する。(ri) Delete "General" on page 72, line l1.
（／θ）同第１４を頁！行のＵペンジルーグ、ｌ−４を
削除して「ベンジルＳ−μ、を−」を挿入する。(/θ) Page 14! Delete the line U Penziroug, l-4 and insert ``Benzil S-μ, wo-''.
（／／）同第１弘頁／り行のｒｌｏ％」の次に「（油中
）」を挿入する。(//) Insert ``(in oil)'' next to ``rlo%'' on the first page of the same page.
（７，２）同第１７頁ｉ〜り行の「／、グｔｒ、 ｇｔ
ｔ−トリス・・・・・・デオキシ」を削除して「λ／
、 ４ｔ′１． ｌ／／−Ｆリスフェニルジチオ−ａｌ
、 ３／護／ 、 ｌｌ−／／ 、 １１１丁ペンタ
デオキシ」を挿入する。(7, 2) "/, gtr, gt on page 17, lines i-ri
t-tris...deoxy" is deleted and "λ/
, 4t'1. l//-F risphenyldithio-al
, 3/Mamoru/ , ll-// , 111 pentadeoxy" is inserted.
ｃ１３）同第１７頁７３行の「チオフェニル・・・・・
・デオキシ」全削除して［フェニルチオ−、、ｉ／ 、
３／ 、 ｐＪ。c13) “Thiophenyl...” on page 17, line 73 of the same
・Deoxy", delete all [phenylthio-,,i/,
3/, pJ.
ｐ／／ 、 ＩＩ／−ペンタデオキシ」を挿入する。p//, II/-pentadeoxy” is inserted.
（／グ）同第１ざ頁３行の「ノＺ ３／ 、 、の次に
［グ′５Ｊを挿入する。(/g) Insert [g'5J next to ``ノZ 3/ , ,'' on the 3rd line of the first page of the same page.
（／ｊ）同第２０頁／行の「２」を「グ」と補正する。(/j) Correct "2" on page 20/line to "gu".
（／６）同第２０頁７〜ｒ行の「炭酸」の次に「（ドラ
イアイス）」を押入する。(/6) Insert "(dry ice)" next to "carbonic acid" on page 20, lines 7 to r.
（／７）同第、２／貞グ〜！行の「ベンノルーグ、２−
」を削除して「ベンノルＳ−≠、２−」を挿入する。(/7) Same number, 2/Sadagu~! Line ``Bennolug, 2-
" and insert "bennol S-≠, 2-".
（１ｇ）同第２／頁７７行、第、２．２頁７．２行及び
第λλ頁／オ行の「ｚ」を「２′」と補正する。(1g) Correct "z" in line 77 of page 2, line 7.2 of page 2.2, and line O of page λλ to "2'".
Ｚ 一般式（Ｉ）
ｔ〃２′
〔式中人は水素原子、または（Ｓ） −４’−アミノ−
Ｊ−ヒド目キシブチリル基を示す〕で表わされる夕。Z General formula (I) t〃2' [The person in the formula is a hydrogen atom, or (S) -4'-amino-
J-represents a xybutyryl group].
、２／ 、 ３／、μ′、グ／／ 、 ７１／ −へ
キサデオキシカナマイシンまたはその／−Ｎ−アシル誘
導体、およびそれらの酸付加塩。, 2/, 3/, μ', g//, 71/ -hexadeoxykanamycin or its /-N-acyl derivative, and acid addition salts thereof.
、！、 ｊ、Ｊ、３’、μ／ 、 ４ｔ／／ 、 ｌ
、／／−ヘキサデオキシカナマイシンし一般式（Ｉ）に
おいて人が水素原子である場合〕である特許請求の範囲
第１項記載の化合物、。,! , j, J, 3', μ/ , 4t// , l
, //-hexadeoxykanamycin, where in general formula (I), human is a hydrogen atom].
、、？、 ／ −Ｎ −（（Ｓ）−グーアミノーーー
ヒドロキシブチリル’Ｊ −、ｔ 、 ２Ｚ ３’、り
ｔ 、 ４／／ 、 ＩＩＩ −へキサデオキシカナ
マイシン〔一般式（Ｄにおいて人が（Ｓ）−ｔ−アミノ
−！−ヒドロキシゾテリル基である場合〕である特許請
求の範囲第１項記載の化合物。,,? , / -N-((S)-guamino-hydroxybutyryl'J-,t,2Z3',rit,4//,III-hexadeoxykanamycin )-t-amino-!-hydroxyzoteryl group].
Claims (1)
−ヒドロキシブチリル基を示す〕で衣わされる５゜２’
、 ３’、 ４’、 ４“、６〃−グートラデオギンカ
ナマイシンまたけその１−Ｎ−アシル誘導体、およびそ
れらの酸イ；１カＩＴＩ霊。 ２、 ５．２’、５’、４’、４’、６’−ヘキサデオ
キシカナマイシンし＝般式（すにおいてＡが水素原子で
ある場合〕である特許請求の範囲第１項記載の化合物。 ３、 １−Ｎ−（（Ｓ）−４−アミノ−２−ヒドロキン
ブチリル） −５、２’、 ３’、 ４’、 ４”、
６’−へキサデオキシカナマイシン〔一般式〔りにおい
て八が（Ｓ） −４−アミノ−２−ヒドロキシブチリル
基である場合〕である特許請求の範囲第１項記載の化合
物。[Claims] 1. General formula (S [wherein A is a hydrogen atom, or (S)-4-amino-2
-5゜2' coated with hydroxybutyryl group]
, 3', 4', 4", 6 - 1-N-acyl derivatives of kanamycin and their acids; 1 KITI. 2, 5.2', 5', 4 ',4',6'-hexadeoxykanamycin = general formula (where A is a hydrogen atom). 3, 1-N-((S)- 4-amino-2-hydroquine butyryl) -5, 2', 3', 4', 4'',
The compound according to claim 1, which is 6'-hexadeoxykanamycin [where 8 is (S)-4-amino-2-hydroxybutyryl group].
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57162292A JPS5953498A (en) | 1982-09-20 | 1982-09-20 | 5,2',3',4',4",6"-hexadeoxykanamycin and its 1-n-acryl derivative |
| US06/532,058 US4486419A (en) | 1982-09-20 | 1983-09-14 | 5,2',3',4',4",6"-Hexadeoxykanamycin and its 1-N-acylated derivative |
| DE8383420151T DE3368640D1 (en) | 1982-09-20 | 1983-09-19 | 5,2',3',4',4",6"-hexadeoxykanamycin and its 1-n-acylated derivative |
| EP83420151A EP0104125B1 (en) | 1982-09-20 | 1983-09-19 | 5,2',3',4',4",6"-hexadeoxykanamycin and its 1-n-acylated derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57162292A JPS5953498A (en) | 1982-09-20 | 1982-09-20 | 5,2',3',4',4",6"-hexadeoxykanamycin and its 1-n-acryl derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5953498A true JPS5953498A (en) | 1984-03-28 |
| JPH024236B2 JPH024236B2 (en) | 1990-01-26 |
Family
ID=15751711
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57162292A Granted JPS5953498A (en) | 1982-09-20 | 1982-09-20 | 5,2',3',4',4",6"-hexadeoxykanamycin and its 1-n-acryl derivative |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US4486419A (en) |
| EP (1) | EP0104125B1 (en) |
| JP (1) | JPS5953498A (en) |
| DE (1) | DE3368640D1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6041692A (en) * | 1983-08-15 | 1985-03-05 | Microbial Chem Res Found | 2',3'-dideoxykanamycin a derivative |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS52153942A (en) * | 1976-06-16 | 1977-12-21 | Microbial Chem Res Found | Preparation of kanamicin c deoxy derivatives and kanamicine c or its deoxy derivatives |
| US4171356A (en) * | 1976-10-28 | 1979-10-16 | Schering Corporation | 2-Unsubstituted derivatives of 4,6-di-o-(aminoglycosyl)-1,3-diaminocyclitois, methods for their use as antibacterial agents and compositions useful therefor |
| JPS55105699A (en) * | 1979-02-05 | 1980-08-13 | Microbial Chem Res Found | 3',4'-dideoxykanamycin a and its 1-n-aminoalkanoyl derivative |
| JPS5643297A (en) * | 1979-09-19 | 1981-04-21 | Microbial Chem Res Found | 6"-deoxydibeckacin or 4",6"-dideoxydibeckacin, their 1-n-acyl derivative, and their preparation |
-
1982
- 1982-09-20 JP JP57162292A patent/JPS5953498A/en active Granted
-
1983
- 1983-09-14 US US06/532,058 patent/US4486419A/en not_active Expired - Fee Related
- 1983-09-19 EP EP83420151A patent/EP0104125B1/en not_active Expired
- 1983-09-19 DE DE8383420151T patent/DE3368640D1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE3368640D1 (en) | 1987-02-05 |
| EP0104125B1 (en) | 1986-12-30 |
| EP0104125A1 (en) | 1984-03-28 |
| JPH024236B2 (en) | 1990-01-26 |
| US4486419A (en) | 1984-12-04 |
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